Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O[C:6]([NH:8][C@H:9]([C:20]([OH:22])=O)[C@@H:10]([CH3:19])[O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:7])(C)(C)C.Cl.[NH2:24][CH2:25][CH2:26][C:27]1[CH:34]=[CH:33][C:31]([OH:32])=[C:29]([OH:30])[CH:28]=1>>[OH:30][C:29]1[CH:28]=[C:27]([CH:34]=[CH:33][C:31]=1[OH:32])[C:6]([NH:8][C@H:9]([C:20]([NH:24][CH2:25][CH2:26][C:27]1[CH:34]=[CH:33][C:31]([OH:32])=[C:29]([OH:30])[CH:28]=1)=[O:22])[C@@H:10]([CH3:19])[O:11][CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)=[O:7]
Reactant: C[C@@H](OCc1ccccc1)[C@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: NCCc1ccc(O)c(O)c1
Agent: Cl
Product: C[C@@H](OCc1ccccc1)[C@H](NC(=O)c1ccc(O)c(O)c1)C(=O)NCCc1ccc(O)c(O)c1
Yield: 120.1 %

Procedure:
The title compound was prepared from Nα-(tert-butoxycarbonyl)-O-benzyl-L-threonine (2.0 g, 6.5 mmol) following the indications of general procedure F using dopamine hydrochloride (2.4 g, 9.7 mmol). The crude material was purified by flash chromatography eluting with 30% EtOAc/CHCl3 to give 2.8 g (98%) of the desired product as white crystals.
Reaction SMILES: [Br:1][C:2]1[C:7]2[C:8](=[O:21])[N:9]3[CH2:20][CH2:19][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16](O)=[O:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1.C(N1C=CN=C1)([N:24]1C=CN=C1)=O.N>CN(C)C=O.O>[Br:1][C:2]1[C:7]2[C:8](=[O:21])[N:9]3[CH2:20][CH2:19][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]([NH2:24])=[O:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: O=C(O)c1ncn2c1[C@@H]1CCN1C(=O)c1c(Br)cccc1-2
Agent: N
Solvent: CN(C)C=O
Solvent: O
Product: NC(=O)c1ncn2c1[C@@H]1CCN1C(=O)c1c(Br)cccc1-2
Reaction time: 0.5 h
Yield: 676.3 %

Procedure:
19.8 g (56.9 mmol) of (S)-8-bromo-9-oxo-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxylic acid were suspended in 100 ml of N,N-dimethylformamide, treated at room temperature with 10.1 g (62.6 mmol) of 1,1'-carbonyldiimidazole and stirred at 70° for 30 minutes. 50 ml of 25% ammonia were added dropwise at 25°-30°. The reaction mixture was diluted with 50 ml of water and cooled to 0°, and the crystallizate was filtered off under suction and dried. There were obtained 133.6 g (69%) of (S)-8-bromo-9-oxo-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxamide of m.p. 314°-317°.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:16]=[CH:17][CH:18]=1)[CH2:6][N:7]1[C:11](=[O:12])[CH2:10][CH2:9][C@@H:8]1[C:13]([OH:15])=O)#[N:2].[NH2:19][CH:20]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH:21]([OH:25])[C:22]([NH2:24])=[O:23].O[NH-].O=[N-]>>[NH2:24][C:22](=[O:23])[C:21](=[O:25])[CH:20]([NH:19][C:13]([C@H:8]1[CH2:9][CH2:10][C:11](=[O:12])[N:7]1[CH2:6][C:5]1[CH:16]=[CH:17][CH:18]=[C:3]([C:1]#[N:2])[CH:4]=1)=[O:15])[CH2:26][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: NC(=O)C(O)C(N)Cc1ccccc1
Reactant: N#Cc1cccc(CN2C(=O)CC[C@@H]2C(=O)O)c1
Agent: [N-]=O
Agent: [NH-]O
Product: N#Cc1cccc(CN2C(=O)CC[C@@H]2C(=O)NC(Cc2ccccc2)C(=O)C(N)=O)c1

Procedure:
Coupling of (R)-1-(3-cyano-benzyl)-5-oxo-pyrrolidine-2-carboxylic acid with 3-amino-2-hydroxy-4-phenylbutanamide and oxidation of the resulting hydroxyamide intermediate to the corresponding ketoamide.
Reaction SMILES: I(C1C=CC=CC=1C(O)=O)(=O)=O.[CH2:13]([N:20]1[C:24](=[O:25])[CH2:23][CH2:22][C@@H:21]1[C:26]([NH:28][CH:29]([CH:37]([OH:44])[C:38]([NH:40][O:41][CH2:42][CH3:43])=[O:39])[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:27])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C([O-])(O)=O.[Na+]>CS(C)=O.O.ClCCl>[CH2:13]([N:20]1[C:24](=[O:25])[CH2:23][CH2:22][C@@H:21]1[C:26]([NH:28][CH:29]([C:37](=[O:44])[C:38]([NH:40][O:41][CH2:42][CH3:43])=[O:39])[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:27])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: CCONC(=O)C(O)C(Cc1ccccc1)NC(=O)[C@H]1CCC(=O)N1Cc1ccccc1
Agent: O=C(O)c1ccccc1I(=O)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Solvent: CS(C)=O
Product: CCONC(=O)C(=O)C(Cc1ccccc1)NC(=O)[C@H]1CCC(=O)N1Cc1ccccc1
Reaction time: 2 h
Yield: 3 %

Procedure:
IBX (2-iodoxybenzoic acid 432 mg, 0.694 mmol) was added to a solution of (2R)-1-benzyl-N-(4-(ethoxyamino)-3-hydroxy-4-oxo-1-phenylbutan-2-yl)-5-oxopyrrolidine-2-carboxamide (218 mg, 0.496 mmol) in DMSO (2 ml). After stiffing for 2 h at room temperature more IBX (123 mg, 0.198 mmol) was added and the stiffing was continued overnight. Saturated aqueous NaHCO3 solution was added and the reaction mixture was diluted with water and dichloromethane. The precipitate formed was filtered off, the organic layer was separated and the aqueous layer extracted with dichloromethane. The combined organic layers were washed with water and dried (MgSO4). The solvent was removed in vacuo, the resulting residue was redissolved in a small amount of dichloromethane and diethylether was added. The white precipitate formed was filtered, washed with diethylether and dried in vacuo. The crude product was dissolved in dichloromethane and treated with three drops of aqueous HCl (4M in dioxane). Removal of the solvent provided the title compound (8.2 mg, 0.015 mmol, 3.02% yield). ESI-MS [M+H]+=438.2
Reaction SMILES: C(OCC(Cl)=O)C1C=CC=CC=1.[CH2:13]([O:20][CH2:21][C:22]([N:24]=[C:25]=[S:26])=[O:23])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH3:27][O:28][C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][C:38]=1[O:39][CH3:40])[N:35]=[CH:34][CH:33]=[C:32]2[O:41][C:42]1[CH:48]=[CH:47][C:45]([NH2:46])=[C:44]([F:49])[CH:43]=1.C1(C)C=CC=CC=1>C(O)C>[CH2:13]([O:20][CH2:21][C:22]([N:24]=[C:25]=[S:26])=[O:23])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH2:13]([O:20][CH2:21][C:22]([NH:24][C:25]([NH:46][C:45]1[CH:47]=[CH:48][C:42]([O:41][C:32]2[C:31]3[C:36](=[CH:37][C:38]([O:39][CH3:40])=[C:29]([O:28][CH3:27])[CH:30]=3)[N:35]=[CH:34][CH:33]=2)=[CH:43][C:44]=1[F:49])=[S:26])=[O:23])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: COc1cc2nccc(Oc3ccc(N)c(F)c3)c2cc1OC
Agent: O=C(COCc1ccccc1)N=C=S
Agent: O=C(Cl)COCc1ccccc1
Solvent: CCO
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3ccc(NC(=S)NC(=O)COCc4ccccc4)c(F)c3)c2cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 43 %

Procedure:
2-(Benzyloxy)ethanoyl isothiocyanate was prepared using commercially available 2-(benzyloxy)ethanoyl chloride (80 mg) as a starting compound according to the description of the literature. 2-(Benzyloxy)ethanoyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (38 mg, yield 43%). Mass spectrometry value (ESI-MS, m/z): 522 (M++1)
Reaction SMILES: [CH3:1][CH:2]([C:10]1[CH:11]=[C:12]([OH:24])[C:13]2[CH2:14][C:15]3[CH2:16][CH2:17][CH2:18][CH2:19][C:20]=3[O:21][C:22]=2[CH:23]=1)[CH:3]([CH3:9])[CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].CC(C1C=C(O)C2C(C)[C:39]3CCC(C)C[C:44]=3[O:45]C=2C=1)C(C)CCCCC>>[C:44]([O:24][C:12]1[C:13]2[CH2:14][C:15]3[CH2:16][CH2:17][CH2:18][CH2:19][C:20]=3[O:21][C:22]=2[CH:23]=[C:10]([CH:2]([CH3:1])[CH:3]([CH3:9])[CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH:11]=1)(=[O:45])[CH3:39]
Reactant: CCCCCC(C)C(C)c1cc(O)c2c(c1)OC1=C(CCC(C)C1)C2C
Reactant: CCCCCC(C)C(C)c1cc(O)c2c(c1)OC1=C(CCCC1)C2
Product: CCCCCC(C)C(C)c1cc(OC(C)=O)c2c(c1)OC1=C(CCCC1)C2

Procedure:
When an equivalent amount of 3-(1,2-dimethylheptyl)-5,6,7,8-tetrahydro-1-hydroxyxanthene is substituted in the procedure of Example 16 for 3-(1,2-dimethylheptyl)-5,6,7,8-tetrahydro-1-hydroxy-6,9-dimethylxanthene, 1-acetoxy-3-(1,2-dimethylheptyl)-5,6,7,8-tetrahydroxanthene is obtained.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1)(=O)[CH3:2].[CH2:10]([N:12]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[N:14]=[C:13]1[NH:21][NH2:22])[CH3:11]>CO.C(O)(=O)C>[CH2:10]([N:12]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[N:14]=[C:13]1[NH:21][N:22]=[C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1)[CH3:2])[CH3:11]
Reactant: CC(=O)c1ccccn1
Reactant: CCn1c(NN)nc2ccccc21
Solvent: CC(=O)O
Solvent: CO
Product: CCn1c(NN=C(C)c2ccccn2)nc2ccccc21
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A mixture of 2-acetyl pyridine (0.62 g, 5.11 mmol) and 1-ethyl-2-hydrazinobenzimidazole (0.90 g, 5.11 mmol) in 20 ml of methanol is stirred at room temperature for 24 hours after the addition of 6 drops of glacial acetic acid. The reaction is monitored by means of thin layer chromatography (Polygram Sil G/UV254 prefabricated foils; eluting agent: CH2Cl2:MeOH (12:1)). Subsequently, the reaction mixture is diluted with distilled water until a precipitate forms and stored for 24 hours in the refrigerator at approximately 5° C. The precipitate is filtered, washed several times with 50% methanol and dried. The product is recrystallized from a mixture of methanol and water. Yield: 0.99 g (70% of theory).
Reaction SMILES: S(=O)(=O)(O)O.[N+:6]([C:9]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:10]=1[C:11]([OH:13])=[O:12])([O-:8])=[O:7].[CH3:22]O>>[N+:6]([C:9]1[CH:17]=[C:16]([C:18]([F:19])([F:20])[F:21])[CH:15]=[CH:14][C:10]=1[C:11]([O:13][CH3:22])=[O:12])([O-:8])=[O:7]
Reactant: CO
Reactant: O=C(O)c1ccc(C(F)(F)F)cc1[N+](=O)[O-]
Agent: O=S(=O)(O)O
Product: COC(=O)c1ccc(C(F)(F)F)cc1[N+](=O)[O-]
Temperature: 25 °C
Yield: 99 %

Procedure:
Add concentrated sulfuric acid (120 mL) dropwise to a solution of 2-nitro-4-trifluoromethylbenzoic acid (200 g, 850 mmol) in methanol (2 L) at room temperature under nitrogen and heat the mixture at reflux for 48 h. Cool the solution to room temperature and remove most of the solvent by evaporation at 45° C. under reduced pressure. Pour the turbid residue onto ice/water (2 L) and extract with ethyl acetate (2×1 L). Wash the combined organic extracts with brine (1 L), dry over anhydrous magnesium sulfate, filter and remove the solvent under reduced pressure to provide the title compound as a yellow oil (212.2 g, >99%). 1H NMR (300 MHz, CDCl3) δ 8.21 (s, 1H), 7.95 (d, J=1.13 Hz, 1H), 7.90 (s, 1H), 3.97 (s, 3H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[F:10])[CH:5]=O.C(O)(=O)[CH2:12][C:13]([OH:15])=[O:14].N1CCCCC1>N1C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:12][C:13]([OH:15])=[O:14])[CH:7]=[CH:8][C:9]=1[F:10]
Reactant: O=Cc1ccc(F)c(Br)c1
Reactant: O=C(O)CC(=O)O
Solvent: C1CCNCC1
Solvent: c1ccncc1
Product: O=C(O)C=Cc1ccc(F)c(Br)c1
Temperature: 100 °C
Reaction time: 3 h
Yield: 54.7 %

Procedure:
3-Bromo-4-fluoro-benzaldehyde (5.0 g, 24.6 mmol), malonic acid (5.6 g, 53.7 mmol), and piperidine (0.5 mL, 4.9 mmol) were added to pyridine (11.4 mL). The reaction mixture was stirred at 100° C. for 3 hours and then concentrated under reduced pressure. Distilled water was added to the reaction mixture, which was then filtered. The resulting solid was recrystallized from ethanol to give 3.3 g of the titled compound as a white solid.
Reaction SMILES: [CH3:1][C:2]1([CH3:24])[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([N:13]3C(=O)C4C(=CC=CC=4)C3=O)=[N:9]2)[CH2:4][O:3]1.CN.CCCCCCC>C(OC)(C)(C)C.C(O)C>[CH3:1][C:2]1([CH3:24])[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([NH2:13])=[N:9]2)[CH2:4][O:3]1
Reactant: CC1(C)OC[C@@H](Cn2ccc(N3C(=O)c4ccccc4C3=O)n2)O1
Agent: CN
Solvent: CCCCCCC
Solvent: CCO
Solvent: COC(C)(C)C
Product: CC1(C)OC[C@@H](Cn2ccc(N)n2)O1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 94.4 %

Procedure:
A suspension of 2-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-isoindole-1,3-dione (5.00 g, 15.3 mmol) in methyl t-butyl ether (50 mL) and ethanol (30 mL) was cooled with an ice water bath, and 33 wt. % methylamine in ethanol (20.0 mL, 161 mmol) was added. After 30 min, the mixture was warmed to room temperature and stirred for 2 h. Heptane (50 mL) was added and the mixture was cooled (−20° C.) for 30 min. The resulting solids were removed by filtration and rinsed with heptane. The filtrate was partially concentrated to a volume of ˜50 mL. The resulting solids were removed by filtration and rinsed with methyl t-butyl ether and heptane. After concentration of the filtrate to dryness, a yellow oil remained, which was then dissolved in methyl t-butyl ether (15 mL) and cooled (−20° C.) for 30 min. Addition of seed crystals and scratching with a spatula initiated crystallization of the product. Heptane (30 mL) was added and the suspension was cooled (−20° C.) for 30 min. Subsequent filtration, washing with heptane, and suction drying afforded 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (2.85 g, 94.6%) as a white solid: LR-ES-MS m/z calculated for C9H15N3O2 [M]+ 197, observed [M+H]+ 198.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([OH:8])[C:3]=1[OH:9].C(=O)([O-])[O-].[K+].[K+].Br[CH2:17][CH2:18]Br.O>CN(C=O)C>[F:1][C:2]1[C:3]2[O:9][CH2:18][CH2:17][O:8][C:4]=2[CH:5]=[CH:6][CH:7]=1
Reactant: BrCCBr
Reactant: Oc1cccc(F)c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Fc1cccc2c1OCCO2
Temperature: 25 °C
Reaction time: 72 h

Procedure:
A solution of 3-fluoro-1,2-benzenediol (5.278 g, 41.2 mmol) in DMF (50 ml) was treated with potassium carbonate (17.08 g, 124 mmol) and 1,2-dibromoethane (3.91 ml, 45.3 mmol) and stirred at rt for 72 h. The reaction was treated with water (200 ml) and extracted 3×200 ml (EtOAc). The combined organic extracts were washed with water (200 ml), brine (200 ml), dried (MgSO4), evaporated and chromatographed (0-20% EtOAc-Cyclohexane) to give product as a clear oil. (2.437 g, 38%).
Reaction SMILES: Br[C:2]1[CH:8]=[C:7]([F:9])[C:5]([NH2:6])=[C:4]([F:10])[CH:3]=1.[CH:11]([O:14][C:15]1[CH:16]=[C:17](B(O)O)[CH:18]=[CH:19][CH:20]=1)([CH3:13])[CH3:12]>>[F:10][C:4]1[CH:3]=[C:2]([C:19]2[CH:18]=[CH:17][CH:16]=[C:15]([O:14][CH:11]([CH3:13])[CH3:12])[CH:20]=2)[CH:8]=[C:7]([F:9])[C:5]=1[NH2:6]
Reactant: CC(C)Oc1cccc(B(O)O)c1
Reactant: Nc1c(F)cc(Br)cc1F
Product: CC(C)Oc1cccc(-c2cc(F)c(N)c(F)c2)c1
Yield: 53.8 %

Procedure:
The title compound (0.34 g) was prepared from 4-Bromo-2,6-difluoro aniline (0.5 g, 2.4 mmol) and 3-isopropoxyphenylboronic acid (0.337 g, 3.1 mmol) as a red liquid. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): 7.30-7.22 (m, 3H), 7.16-7.07 (m, 2H), 6.89 (dd, J 2.3, 8.1, 1H), 5.32 (s, 2H), 4.68 (septet, J 6, 1H), 1.26 (d, J 6, 6H).
Reaction SMILES: COC([C:5]1[N:6]=[C:7]([C:23]#[N:24])[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:9]=2)=O.[CH3:25][O-:26].[Na+].[CH3:28][OH:29].Cl.[CH3:31][OH:32]>O>[CH3:25][O:26][C:31](=[O:32])[C:13]([CH3:8])([CH3:12])[CH2:14][CH2:5][NH:6][C:28]([C:5]1[N:6]=[C:7]([C:23]#[N:24])[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:9]=2)=[O:29]
Reactant: CO
Reactant: COC(=O)c1nc(C#N)c2cc(Oc3ccccc3)ccc2c1O
Reactant: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Product: COC(=O)C(C)(C)CCNC(=O)c1nc(C#N)c2cc(Oc3ccccc3)ccc2c1O
Yield: 19 %

Procedure:
To a mixture of 1-cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (90 mg, 0.28 mmol) and 4-amino-2,2-dimethyl-butyric acid methyl ester, trifluoroacetic acid salt (290 mg, 1.12 mmol) in MeOH (0.5 mL) was added 0.5 M NaOMe/MeOH solution until the pH of the mixture reaches 8 (1.24 mL, 0.61 mmol was added). The resultant mixture was refluxed overnight. Reaction mixture was diluted with water (50 mL), acidified by 1 N HCl to pH=4 and then extracted with EtOAc. Organic layer was washed with brine, dried over MgSO4, filtered and concentrated. Residue was purified by silica gel chromatography, eluting with 5-50% EtOAc/hexnaes. Fractions containing the desired product were collected and concentrated. The resultant solid was triturated with MeOH (2 mL). Solid was collected and dried in vacuo to provide the title compound 23 mg (0.053 mmol) in 19% yield. LC-MS ESI−: 432.13 (M−1)−.
Reaction SMILES: [CH3:1][N:2]([CH3:28])[C:3]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:8][CH2:7][C:6](=[CH:9][C:10]([NH:12][CH2:13][CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:11])[CH2:5][CH2:4]1.[Cl:29][Si](C)(C)C>CC(CC)=O>[ClH:29].[CH3:28][N:2]([CH3:1])[C:3]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:8][CH2:7][C:6](=[CH:9][C:10]([NH:12][CH2:13][CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:11])[CH2:5][CH2:4]1
Reactant: C[Si](C)(C)Cl
Agent: CN(C)C1(c2ccccc2)CCC(=CC(=O)NCCCc2ccccc2)CC1
Solvent: CCC(C)=O
Product: Cl
Reaction time: 2 h

Procedure:
2-(4-Dimethylamino-4-phenylcyclohexylidene)-N-(3-phenyl-propyl)acetamide (203 mg, 0.536 mmol) was dissolved in ethyl methyl ketone (12 ml) with gentle heating and chlorotrimethylsilane (0.101 ml, 0.8 mmol) was added. After 2 h it was possible to isolate the product as a colourless solid in a yield of 95% (211 mg) with an m.p. of 225-230° C.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[NH2:12])[C:5]([O:7][CH3:8])=[O:6].C(=O)([O-])[O-].[K+].[K+].[Cl:19][C:20]1[CH:29]=[CH:28][C:23]([CH:24]=[CH:25][CH2:26]Cl)=[CH:22][CH:21]=1>CN(C)C=O>[NH2:12][C:11]1[CH:10]=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]=1[NH:1][CH2:26][CH:25]=[CH:24][C:23]1[CH:28]=[CH:29][C:20]([Cl:19])=[CH:21][CH:22]=1
Reactant: ClCC=Cc1ccc(Cl)cc1
Reactant: COC(=O)c1ccc(N)c(N)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(N)c(NCC=Cc2ccc(Cl)cc2)c1
Yield: 63.2 %

Procedure:
5.0 g of methyl 3,4-diaminobenzoate was dissolved in 40 ml of dimethylformamide, and to the solution were added 2.07 g of potassium carbonate and 1.87 g of p-chlorocinnamyl chloride, and reaction was carried out according to the procedure in Reference Example 40, to obtain 2.0 g of the title compound as a light brown oil.
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([C@H:10]2[CH2:15][CH2:14][C@H:13]([CH2:16][CH2:17][CH3:18])[CH2:12][CH2:11]2)=[CH:6][CH:5]=1)[CH2:2][CH3:3]>C(O)C.O=[Pt]=O>[CH2:16]([CH:13]1[CH2:14][CH2:15][CH:10]([CH:7]2[CH2:6][CH2:5][CH:4]([CH2:1][CH2:2][CH3:3])[CH2:9][CH2:8]2)[CH2:11][CH2:12]1)[CH2:17][CH3:18]
Reactant: CCCc1ccc([C@H]2CC[C@H](CCC)CC2)cc1
Agent: O=[Pt]=O
Solvent: CCO
Product: CCCC1CCC(C2CCC(CCC)CC2)CC1

Procedure:
A solution of 24.4 g of trans-1-p-propylphenyl-4-propylcyclohexane in 500 ml of ethanol is hydrogenated over 1 g of PtO2 for 1 hour at 60° and 100 bar, and the mixture is cooled, filtered and evaporated to give 4,4'-dipropylbicyclohexyl in the form of an oily mixture of isomers, which is taken up in 200 ml of boiling methanol. The resulting hot solution is poured into a boiling solution of 70 g of thiourea in 300 ml of methanol. The mixture is cooled to 0°, and the adduct which has been precipitated is filtered off and extracted by boiling with 300 ml of petroleum ether (b.p. 40°-60°). The undissolved residue is heated with 350 ml of 2N aqueous potassium hydroxide solution for 30 minutes at 50°. The solution is acidified with H2SO4 to give, after customary working up, trans,trans-4,4'-dipropylbicyclohexyl, c.p. 41°.
Reaction SMILES: [C:1]([O:5][C:6]([C:8]1([CH2:19][C:20]#[C:21][CH2:22][CH3:23])[C:12](=[O:13])[CH:11]=[CH:10][CH:9]1[CH2:14][C:15]([O:17][CH3:18])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H]>CC(C)=O.[Pd].CC([O-])=O.CC([O-])=O.[Pb+2]>[C:1]([O:5][C:6]([C:8]1([CH2:19]/[CH:20]=[CH:21]\[CH2:22][CH3:23])[C:12](=[O:13])[CH:11]=[CH:10][CH:9]1[CH2:14][C:15]([O:17][CH3:18])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: [H][H]
Reactant: CCC#CCC1(C(=O)OC(C)(C)C)C(=O)C=CC1CC(=O)OC
Agent: [Pd]
Agent: CC(=O)[O-]
Agent: [Pb+2]
Solvent: CC(C)=O
Product: CC/C=C\CC1(C(=O)OC(C)(C)C)C(=O)C=CC1CC(=O)OC

Procedure:
A 4.5 g quantity of 5-methoxycarbonyl-4-methoxycarbonylmethyl-5-(2-pentynyl)-2-cyclopentenone (compound (1-a)) is dissolved in a mixture of 50 ml of n-hexhane and 50 ml of acetone, and 7 g of a Lindlar catalyst is added to the solution. Hydrogen gas is introduced into the solution with stirring. The reaction is completed when the solution has absorbed the theoretical amount of the gas. On completion of the reaction, the catalyst is filtered off from the reaction mixture, and the filtrate is concentrated at reduced pressure. The residue is distilled in a vacuum, affording 5-methoxycarbonyl-4-methoxycarbonylmethyl-5-(cis-2-pentenyl)-2-cyclopentenone (compound (1-b), R1 =CH3, R2 =CH3) in a yield of 99.8%, b.p. 81°-85° C./0.005 mm Hg.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=2)[CH:10]=[C:9]1[C:19](O)([CH3:21])[CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.CCOCC>CCOC(C)=O.CCO.[Pd]>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=2)[CH:10]=[C:9]1[CH:19]([CH3:21])[CH3:20])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc2cc(C(C)(C)O)n(Cc3ccccc3)c2c1
Agent: [Pd]
Agent: Cl
Solvent: CCOCC
Solvent: CCOC(C)=O
Solvent: CCO
Product: COc1ccc2cc(C(C)C)n(Cc3ccccc3)c2c1
Reaction time: 1 h

Procedure:
To a solution of 2-(1-benzyl-6-methoxy-1H-indol-2-yl)propan-2-ol (Compound 3, 1.05 g, 3.57 mmol) in EtOAc (35 ml) and EtOH (15 ml) was added 10% Pd—C (190 mg, 0.18 mmol) and HCl-Et2O (1.0 M, 1.25 ml, 1.25 mmol). The mixture was stirred under hydrogen gas (atmospheric pressure) for 1 h and was filtered. To the filtrate was added NaHCO3 (0.5 g) and H2O (0.5 ml), followed by Na2SO4 and MgSO4. This was then filtered and concentrated in vacuo to yield the crude title compound as a yellow solid.
Reaction SMILES: [OH:1][CH:2]1[CH2:7][C:6]([CH3:9])([CH3:8])[O:5][C:3]1=[O:4].[C:10](Cl)(=[O:14])[C:11]([CH3:13])=[CH2:12].C(N(CC)CC)C.C1(C)C=CC=CC=1>O>[C:10]([O:1][CH:2]1[CH2:7][C:6]([CH3:9])([CH3:8])[O:5][C:3]1=[O:4])(=[O:14])[C:11]([CH3:13])=[CH2:12]
Reactant: CC1(C)CC(O)C(=O)O1
Reactant: C=C(C)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Solvent: O
Product: C=C(C)C(=O)OC1CC(C)(C)OC1=O
Temperature: 25 °C
Reaction time: 4 h
Yield: 85 %

Procedure:
A mixture of 100 mmole of the above-prepared 2-hydroxy4,4-dimethyl-γ-butyrolactone, 150 mmole of methacrylic chloride, 150 mmole of triethylamine, and 300 ml of toluene was stirred at 25° C. for 4 hours. Water was added to the reaction mixture, the organic layer was then concentrated, and the concentrate was subjected to column chromatography on a silica gel to yield 2-methacryloyloxy-4,4-dimethyl-γ-butyrolactone in a yield of 85%.
Reaction SMILES: C([O:8][CH2:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([C:18]2[CH:23]=[CH:22][C:21]([N:24]3[CH2:28][C@H:27]([CH2:29][NH:30][C:31](=[O:33])[CH3:32])[O:26][C:25]3=[O:34])=[CH:20][C:19]=2[F:35])[CH2:14][CH2:13]1)=[O:11])C1C=CC=CC=1>CO.[OH-].[OH-].[Pd+2]>[OH:8][CH2:9][C:10]([N:12]1[CH2:13][CH2:14][CH:15]([C:18]2[CH:23]=[CH:22][C:21]([N:24]3[CH2:28][C@H:27]([CH2:29][NH:30][C:31](=[O:33])[CH3:32])[O:26][C:25]3=[O:34])=[CH:20][C:19]=2[F:35])[CH2:16][CH2:17]1)=[O:11]
Reactant: CC(=O)NC[C@H]1CN(c2ccc(C3CCN(C(=O)COCc4ccccc4)CC3)c(F)c2)C(=O)O1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: CC(=O)NC[C@H]1CN(c2ccc(C3CCN(C(=O)CO)CC3)c(F)c2)C(=O)O1
Reaction time: 4 h

Procedure:
A mixture of (S)-(-)-N-[[3-[4-[1-[(benzyloxy)acetyl]-4-piperidinyl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (EXAMPLE 21, 5.00 g) and 20% palladium hydroxide on carbon (2.80 g) in methanol 500 mL) is stirred under a hydrogen atmosphere (balloon) for four hours, the catalyst is removed by filtration through Celite and the filtrate is concentrated under reduced pressure, triturated with methylene chloride/diethyl ether and filtered to give the title compound, mp 182-183° C.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[CH:6][C:7](F)=[C:8]([S:10]([NH2:13])(=[O:12])=[O:11])[CH:9]=1)(=[O:3])[CH3:2].[NH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1>C(O)C>[C:1]([C:4]1[CH:5]=[CH:6][C:7]([N:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)=[C:8]([S:10]([NH2:13])(=[O:12])=[O:11])[CH:9]=1)(=[O:3])[CH3:2]
Reactant: C1CCNCC1
Reactant: CC(=O)c1ccc(F)c(S(N)(=O)=O)c1
Solvent: CCO
Product: CC(=O)c1ccc(N2CCCCC2)c(S(N)(=O)=O)c1

Procedure:
A solution of 5-acetyl-2-fluorobenzenesulphonamide (1 g) and piperidine (0.98 g) in ethanol (50 ml) was heated under reflux for 3.5 hours. The solvent was removed and the residue was dissolved in ethyl acetate (100 ml) and washed with water (2 × 100 ml). The organic phase was dried (MgSO4) and concentrated and the product was crystallised from isopropanol, 0.92 g, m.p. 130.5°-131.5°.